A Gap Door in Cancer Treatment Trials

This article was originally published by Undark magazine.

Updated at 4:04 pm ET on July 5, 2023

In October 2021, 84-year-old Jim Yeldell was diagnosed with Stage 3 lung cancer. The first drug he tried interfered with his balance and coordination, so his doctor reduced the dose to reduce these complications, Yeldell recalls. In addition, her doctor recommended that she be given a combination of antibiotics, chemotherapy, and gene therapy. This combination can be very effective, especially in young people, but it can be “very toxic” in older, frail people, said Elizabeth Kvale, a palliative care specialist at Baylor College of Medicine, and Yeldell’s daughter-in-law.

Elderly patients are often underrepresented in clinical trials of new cancer drugs, including those offered to Yeldell. As a result, he only learned about the potential for toxicity because his son-in-law saw the adverse effects of the drug on adults at his clinic.

This lack of age-related data has significant implications for clinical care, as older adults are more likely to be diagnosed with cancer than younger adults. In the US, approx 42 percent of people with cancer are over 70 years old—a number that will grow in the coming years—yet they make up less than a third of people who are screened for it. new cancer drugs. Most of the participants are healthy seniors, who may not have age-related diseases such as diabetes or poor kidney or heart function, said Mina Sedrak, an oncologist and director of the Cancer and Aging program at the University. in California Los Angeles.

For years, clinical trials have excluded older people for reasons that include concerns about pre-existing conditions and other medications and the ability of participants to attend the trial. As a result, doctors cannot be sure that approved cancer drugs work as predicted in clinical trials in people with cancer. This lack of data means that elderly cancer patients must decide whether they want to receive a treatment that may bring less benefit – and cause more side effects – than young people did in clinical trials.

This disparity in evidence spans all types of cancer treatments—from chemotherapy and radiation to immune-checkpoint inhibitors—and sometimes adverse outcomes. Many types of chemotherapy, for example, have been shown to be highly toxic in older people, a discovery that came after the drug was approved for use in this population. “This is a big problem,” says Sedrak. In order to reduce the side effects, doctors often do it change the level or the length of the medication given to the elderly, but these doctors are doing this without any real guidance.

Even the advice from donors and controllersalso to spread the word, not much has changed in the past three decades. “We’re at a point where everyone agrees it’s a problem, but there’s very little guidance on how to do it right for adults,” says Kvale. “The consequences in the real world are dire.”

Post-approval studies of cancer drugs have helped highlight discrepancies between how drugs are used in clinical trials and how they are used in hospitals around the country.

For example, when Cary Gross, a physician and cancer researcher at Yale, began studying the use of a new type of cancer drug called an immune-checkpoint inhibitor, he learned that many doctors knew that clinical trials were ignoring elderly patients. . Gross’s research team speculates that some doctors may be wary of giving the elderly the treatment, which works by preventing immune cells from dying, thereby allowing them to kill cancer cells. “Maybe they will be more careful,” he says, and give first aid to young patients.

But in 2018 analysis of more than 3,000 patients, Gross and colleagues found that within four months of FDA approval, most patients eligible to receive a class of immune-checkpoint inhibitors were being prescribed the drug. And the patients who received this treatment in hospitals were significantly older than those who were tested in the hospital. “Oncologists were more willing to offer the drug to older patients, even though they are underrepresented,” says Gross.

In further analysis, published this year, Gross and his colleagues investigated how the drug helped people with certain types of lung cancer. The team found that the drug extended life in patients under 55 by an average of four and a half months, but by one month in those over 75.

The evidence doesn’t mean that checkpoint inhibitors don’t help most patients, Gross says. But it is important to know which people are most helped by this medicine. He said: “I thought we would survive more than we did.” “It calls into question the way we do research, and we need to do more research including older patients.”

People over the age of 65 do not respond well to certain types of cancer treatment. About half of elderly patients with advanced cancer experience complications and even potentially life-threatening side effects with chemotherapy, which can cause oncologists to reduce the dose of drugs, as was the case with Yeldell.

There is a strong correlation between the lack of evidence from clinical trials and poor clinical outcomes, according to Kvale. “There’s a lot of excitement about these drugs that don’t seem very dangerous going forward,” he says, “but understanding where they’re working or not working well is important—not just because of their effectiveness, but because the drugs are effective.” almost too expensive sometimes. “

Since the initial reports of this data discrepancy, regulators and researchers have attempted to correct the problem. Changes in clinical trials, in particular, have made it easier for older adults to enroll. For example, minority and minority studies have age limits for participants. Last year, the FDA issued guidance to industry-sponsored trials that recommend that older adults be combined with other relaxation techniques, to allow participants with age-related cognitive decline. However, the problem persists.

As Sedrak and his colleagues began to understand why the needle had moved so little over the past few decades, analysis found several explanations, starting with appropriate measures that may prevent the elderly from knowing it. Doctors may also be concerned about the ability of their elderly patients to tolerate the unknown side effects of new drugs. Patients and caregivers share these concerns. Planning for participation can also be difficult.

“But of all of this, the main driving force, the upper hand, is that the tests were not designed with older adults in mind,” says Sedrak. Clinical trials tend to focus on survival, and although older adults care about this, many of them have other motivations – and concerns – for considering treatment.

Clinical trials often focus on measuring changes in health: They can track the growth of tumors or months of life gained. These issues are not as difficult for adults, according to Sedrak. He says he can hear questions about how the results will affect the patient’s cognition, independent living, and more. “We don’t create tests that capture the facts that adults want to know,” he says.

As a group, the elderly face many problems, sometimes so severe that medicine is against the disease. In the absence of evidence from clinical trials, doctors and patients have tried to find other ways to determine how a patient’s age can affect how they will respond to treatment. In Yeldell’s case, discussions with Kvale and his care team led him to choose the least invasive treatment that has made his cancer stable since October 2022. He continues to live at home and exercise with a trainer three times a week.

For some who are trying to test their options, researchers are developing tools that can provide a complete picture of how to calculate the age of a person’s body. In 2021 clinical trials, Supriya Mohile, a geriatric oncologist at the University of Rochester, and colleagues tested one such tool, known as the geriatric assessment, on the side effects and toxicity of cancer drugs. The tool assesses a person’s natural age based on various physical tests.

The team recruited more than 700 people with an average age of 77 who were about to start a new treatment for cancer with a high risk of toxicity. About half of the participants received treatment management guidelines based on patient evaluations, which their oncologists incorporated into their treatment decisions. Only half of this group of patients experienced adverse effects from chemotherapy, compared to 71 percent of those who did not receive chemotherapy.

Such screening could help prevent overtreatment of people who might benefit from chemotherapy and increase the risk of adverse effects, says Mohile. It does not compensate for the lack of data on adults. But in the absence of that evidence, tools like patient assessments can help clinicians, patients, and families make informed decisions. “We are going backwards from this problem,” says Mohile. Although oncologists recognize the importance of having good decision-making processes, he says, “I think that patient evaluation should be done until we have enough clinical information.”

Since 2018, the American Society of Clinical Oncology has recommended the use of geriatric assessment to guide cancer care for elderly patients. But doctors have been slow to follow their practice, in part because of the evaluation it doesn’t show any cancer-related benefits, such as shrinking tumors and people living longer. In fact, the main purpose of the tool is to improve the quality of life. “We need more clinical trials for older adults, but we also need all these other options to get funding,” says Mohile, “So we know what to do with older adults in the real world.”

Due to an editing error, the story messed with Mina Sedrak’s relationship.

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